Acitretin

Molecule Info

Acitretin must not be used by females who are pregnant, or who intend to become pregnant during therapy or at any time for at least 3 years following discontinuation of therapy. Acitretin also must not be used by females who may not use reliable contraception while undergoing treatment and for at least 3 years following discontinuation of treatment. Acitretin is a metabolite of etretinate (TegisonÂ®), and major human fetal abnormalities have been reported with the administration of acitretin and etretinate. Potentially, any fetus exposed can be affected.

Clinical evidence has shown that concurrent ingestion of acitretin and ethanol has been associated with the formation of etretinate, which has a significantly longer elimination half-life than acitretin. Because the longer elimination half-life of etretinate would increase the duration of teratogenic potential for female patients, ethanol must not be ingested by female patients either during treatment with Acitretin or for 2 months after cessation of therapy. This allows for elimination of acitretin, thus removing the substrate for transesterification to etretinate. The mechanism of the metabolic process for conversion of acitretin to etretinate has not been fully defined. It is not known whether substances other than ethanol are associated with transesterification.

Acitretin has been shown to be embryotoxic and/or teratogenic in rabbits, mice, and rats at oral doses of 0.6, 3 and 15 mg/kg, respectively. These doses are approximately 0.2, 0.3 and 3 times the maximum recommended therapeutic dose, respectively, based on a mg/m2 comparison.

Acitretin should be prescribed only by those who have special competence in the diagnosis and treatment of severe psoriasis, are experienced in the use of systemic retinoids, and understand the risk of teratogenicity.

Because of Acitretin'steratogenicity, a program called the Do Your P.A.R.T program, Pregnancy Prevention Actively Required During and After Treatment, has been developed to educate women of childbearing potential and their healthcare providers about the serious risks associated with acitretin and to help prevent pregnancies from occurring with the use of this drug and for 3 years after its discontinuation. The Do Your P.A.R.T. program requirements are described below.

Important Information for Women of Childbearing Potential:

Acitretin should be considered only for women with severe psoriasis unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments.

Females of reproductive potential must not be given a prescription for Acitretin until pregnancy is excluded. Acitretin is contraindicated in females of reproductive potential unless the patient meets ALL of the following conditions:

â€¢ Must have had 2 negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial Acitretin prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue Acitretin therapy. The second pregnancy test (a confirmation test) should be done during the first 5 days of the menstrual period immediately preceding the beginning of Acitretin therapy. For patients with amenorrhea, the second test should be done at least 11 days after the last act of unprotected sexual intercourse (without using 2 effective forms of contraception [birth control] simultaneously).

â€¢ Must have a pregnancy test repeated every month during Acitretin treatment. The patient must have a negative result from a urine or serum pregnancy test before receiving a Acitretin prescription. To encourage compliance with this recommendation, a limited supply of the drug should be prescribed. For at least 3 years after discontinuing Acitretin therapy, a pregnancy test must be repeated every 3 months.

â€¢ Must have selected and have committed to use 2 effective forms of contraception (birth control) simultaneously, at least 1 of which must be a primary form, unless absolute abstinence is the chosen method, or the patient has undergone a hysterectomy or is clearly postmenopausal.

â€¢ Patients must use 2 effective forms of contraception (birth control) simultaneously for at least 1 month prior to initiation of Acitretin therapy, during Acitretin therapy, and for at least 3 years after discontinuing Acitretin therapy. A Acitretin Patient Referral Form is available so that patients can receive an initial free contraceptive counseling session and pregnancy testing. Counseling about contraception and behaviors associated with an increased risk of pregnancy must be repeated on a monthly basis by the prescriber during Acitretin therapy and every 3 months for at least 3 years following discontinuation of Acitretin therapy.

Effective forms of contraception include both primary and secondary forms of contraception. Primary forms of contraception include: tubal ligation, partner's vasectomy, intrauterine devices, birth control pills, and injectable/implantable/insertable/topical hormonal birth control products. Secondary forms of contraception include latex condoms (with or without spermicide), diaphragms and cervical caps (which must be used with a spermicide).

Any birth control method can fail. Therefore, it is critically important that women of childbearing potential use 2 effective forms of contraception (birth control) simultaneously. It has not been established if there is a pharmacokinetic interaction between acitretin and combined oral contraceptives. However, it has been established that acitretin interferes with the contraceptive effect of microdosed progestin preparations#. Microdosed â€œminipillâ€ progestin preparations are not recommended for use with Acitretin. It is not known whether other progestational contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.

Prescribers are advised to consult the package insert of any medication administered concomitantly with hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John's Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John's Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John's Wort.

â€¢ Must have signed a Patient Agreement/Informed Consent for Female Patients that contains warnings about the risk of potential birth defects if the fetus is exposed to Acitretin, about contraceptive failure, about the fact that they must not ingest beverages or products containing ethanol while taking Acitretin and for 2 months after Acitretin treatment has been discontinued, and about preventing pregnancy while taking Acitretin and for at least 3 years after discontinuing Acitretin therapy.

If pregnancy does occur during Acitretin therapy or at any time for at least 3 years following discontinuation of Acitretin therapy, the prescriber and patient should discuss the possible effects on the pregnancy. The available information is as follows:

Acitretin, the active metabolite of etretinate, is teratogenic and is contraindicated during pregnancy. The risk of severe fetal malformations is well established when systemic retinoids are taken during pregnancy. Pregnancy must also be prevented after stopping acitretin therapy, while the drug is being eliminated to below a threshold blood concentration that would be associated with an increased incidence of birth defects. Because this threshold has not been established for acitretin in humans and because elimination rates vary among patients, the duration of posttherapy contraception to achieve adequate elimination cannot be calculated precisely. It is strongly recommended that contraception be continued for at least 3 years after stopping treatment with acitretin, based on the following considerations:

â€¢ In the absence of transesterification to form etretinate, greater than 98% of the acitretin would be eliminated within 2 months, assuming a mean elimination half-life of 49 hours.

â€¢ In cases where etretinate is formed, as has been demonstrated with concomitant administration of acitretin and ethanol,

â€¢ greater than 98% of the etretinate formed would be eliminated in 2 years, assuming a mean elimination half-lie of 120 days.

â€¢ greater than 98% of the etretinate formed would be eliminated in 3 years, based on the longest demonstrated elimination half-life of 168 days.

However, etretinate was found in plasma and subcutaneous fat in one patient reported to have had sporadic alcohol intake, 52 months after she stopped acitretin therapy#.

â€¢ Severe birth defects have been reported where conception occurred during the time interval when the patient was being treated with acitretin and/or etretinate. In addition, severe birth defects have also been reported when conception occurred after the mother completed therapy. These cases have been reported both prospectively (before the outcome was known) and retrospectively (after the outcome was known). The events below are listed without distinction as to whether the reported birth defects are consistent with retinoid-induced embryopathy or not.

â€¢ There have been 318 prospectively reported cases involving pregnancies and the use of etretinate, acitretin or both. In 238 of these cases, the conception occurred after the last dose of etretinate (103 cases), acitretin (126) or both (9). Fetal outcome remained unknown in approximately one-half of these cases, of which 62 were terminated and 14 were spontaneous abortions. Fetal outcome is known for the other 118 cases and 15 of the outcomes were abnormal (including cases of absent hand/wrist, clubfoot, GI malformation, hypocalcemia, hypotonia, limb malformation, neonatal apnea/anemia, neonatal ichthyosis, placental disorder/death, undescended testicle and 5 cases of premature birth). In the 126 prospectively reported cases where conception occurred after the last dose of acitretin only, 43 cases involved conception at least 1 year but less than 2 years after the last dose. There were 3 reports of abnormal outcomes out of these 43 cases (involving limb malformation, GI tract malformations and premature birth). There were only 4 cases where conception occurred at least 2 years after the last dose but there were no reports of birth defects in these cases.

â€¢ There is also a total of 35 retrospectively reported cases where conception occurred at least one year after the last dose of etretinate, acitretin or both. From these cases there are 3 reports of birth defects when the conception occurred at least 1 year but less than 2 years after the last dose of acitretin (including heart malformations, Turner's Syndrome, and unspecified congenital malformations) and 4 reports of birth defects when conception occurred 2 or more years after the last dose of acitretin (including foot malformation, cardiac malformations [2 cases] and unspecified neonatal and infancy disorder). There were 3 additional abnormal outcomes in cases where conception occurred 2 or more years after the last dose of etretinate (including chromosome disorder, forearm aplasia, and stillbirth).

Females who have taken Tegison (etretinate) must continue to follow the contraceptive recommendations for Tegison.

Patients should not donate blood during and for at least 3 years following the completion of Acitretin therapy because women of childbearing potential must not receive blood from patients being treated with Acitretin.

Important Information For Males Taking Acitretin:

Patients should not donate blood during and for at least 3 years following Acitretin therapy because women of childbearing potential must not receive blood from patients being treated with Acitretin.

Samples of seminal fluid from 3 male patients treated with acitretin and 6 male patients treated with etretinate have been assayed for the presence of acitretin. The maximum concentration of acitretin observed in the seminal fluid of these men was 12.5 ng/mL. Assuming an ejaculate volume of 10 mL, the amount of drug transferred in semen would be 125 ng, which is 1/200,000 of a single 25 mg capsule. Thus, although it appears that residual acitretin in seminal fluid poses little, if any, risk to a fetus while a male patient is taking the drug or after it is discontinued, the no-effect limit for teratogenicity is unknown and there is no registry for birth defects associated with acitretin. The available data are as follows:

There have been 25 cases of reported conception when the male partner was taking acitretin. The pregnancy outcome is known in 13 of these 25 cases. Of these, 9 reports were retrospective and 4 were prospective (meaning the pregnancy was reported prior to knowledge of the outcome)#.

Severe forms of psoriasis including erythrodermic psoriasis; local or generalized pustular psoriasis. Severe disorders of keratinization eg congenital ichthyosis; pityriasis rubra pilaris; Darier's disease; other disorders of keratinization which may be resistant to other therapies.

Hepatotoxicity:Of the 525 patients treated in US clinical trials, 2 had clinical jaundice with elevated serum bilirubin and transaminases considered related to Soriatane treatment. Liver function test results in these patients returned to normal after Soriatane was discontinued. Two of the 1289 patients treated in European clinical trials developed biopsy-confirmed toxic hepatitis. A second biopsy in one of these patients revealed nodule formation suggestive of cirrhosis. One patient in a Canadian clinical trial of 63 patients developed a three-fold increase of transaminases. A liver biopsy of this patient showed mild lobular disarray, multifocal hepatocyte loss and mild triaditis of the portal tracts compatible with acute reversible hepatic injury. The patient's transaminase levels returned to normal 2 months after Soriatane was discontinued.

The potential of Soriatane therapy to induce hepatotoxicity was prospectively evaluated using liver biopsies in an open-label study of 128 patients. Pretreatment and posttreatment biopsies were available for 87 patients. A comparison of liver biopsy findings before and after therapy revealed 49 (58%) patients showed no change, 21 (25%) improved and 14 (17%) patients had a worsening of their liver biopsy status. For 6 patients, the classification changed from class 0 (no pathology) to class I (normal fatty infiltration; nuclear variability and portal inflammation; both mild); for 7 patients, the change was from class I to class II (fatty infiltration, nuclear variability, portal inflammation and focal necrosis; all moderate to severe); and for 1 patient, the change was from class II to class IIIb (fibrosis, moderate to severe). No correlation could be found between liver function test result abnormalities and the change in liver biopsy status, and no cumulative dose relationship was found.

Elevations of AST (SGOT), ALT (SGPT), GGT (GGTP) or LDH have occurred in approximately 1 in 3 patients treated with Soriatane. Of the 525 patients treated in clinical trials in the US, treatment was discontinued in 20 (3.8%) due to elevated liver function test results. If hepatotoxicity is suspected during treatment with Soriatane, the drug should be discontinued and the etiology further investigated.

Ten of 652 patients treated in US clinical trials of etretinate, of which acitretin is the active metabolite, had clinical or histologic hepatitis considered to be possibly or probably related to etretinate treatment. There have been reports of hepatitis-related deaths worldwide; a few of these patients had received etretinate for a month or less before presenting with hepatic symptoms or signs.

Brand/Product Info

Gen. MedInfo

IMPORTANT WARNING:

For female patients:

Do not take acitretin if you are pregnant or plan to become pregnant within the next 3 years. Acitretin may harm the fetus. You should not begin taking acitretin until you have taken two pregnancy tests with negative results. You must use two acceptable forms of birth control for 1 month before you begin taking acitretin, during your treatment with acitretin, and for 3 years after treatment. Your doctor will inform you which methods of birth control are acceptable. You do not need to use two methods of birth control if you have had a hysterectomy (surgery to remove the womb), if your doctor informs you that you have finished menopause (change of life), or if you practice total sexual abstinence.

If you plan to use oral contraceptives (birth control pills) while taking acitretin, inform your doctor the name of the pill you will use. Acitretin interferes with the action of microdosed progestin ('minipill') oral contraceptives (Ovrette, Micronor, Nor-QD). Do not use this type of birth control while taking acitretin.

If you plan to use hormonal contraceptives (birth control pills, patches, implants, injections, and intrauterine devices), be sure to inform your doctor about all the medications, vitamins, and herbal supplements you are taking. Many medications interfere with the action of hormonal contraceptives. Do not take St. John's wort if you are using any type of hormonal contraceptive.

You will need to take pregnancy tests regularly while taking acitretin. Stop taking acitretin and call your doctor immediately if you become pregnant, miss a menstrual period, or have sex without using two forms of birth control. In some cases, your doctor can prescribe emergency contraception ('the morning after pill') to prevent pregnancy.

Do not consume foods, drinks, or prescription or nonprescription medications that contain alcohol while taking acitretin and for 2 months after treatment. Alcohol and acitretin combine to form a substance that remains in the blood for a long time and can harm the fetus. Read medication and food labels carefully and ask your doctor if you are not sure whether a medication contains alcohol.

Your doctor will give you a Patient Agreement/Informed Consent to read and sign before you begin treatment. Be sure to read this carefully and ask your doctor if you have any questions.

For male patients:

A small amount of acitretin is present in the semen of male patients who take this medication. It is not known whether this small amount of medication can harm the fetus. Talk to your doctor about the risks of taking this medication if your partner is pregnant or plans to become pregnant.

For male and female patients:

Do not donate blood while taking acitretin and for 3 years after treatment.

Acitretin may cause liver damage. inform your doctor if you have or have ever had liver disease. If you experience any of the following symptoms, call your doctor immediately: upset stomach, extreme tiredness, unusual bruising or bleeding, lack of energy, loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, dark urine, or flu-like symptoms.

Why is this medication prescribed?

Acitretin is used to treat severe psoriasis (abnormal growth of skin cells that causes red, thickened, or scaly skin). Acitretin is in a class of medications called retinoids. The way acitretin works is not known.

How should this medicine be used?

Acitretin may come as a capsule to take by mouth. It is usually taken once a day with the main meal. Take acitretin at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor to explain any part you do not understand. Take acitretin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may start you on a low dose of acitretin and gradually increase your dose.

Acitretin controls psoriasis but does not cure it. It may take 2-3 months or longer before you feel the full benefit of acitretin. Your psoriasis may get worse during the first few months of treatment. This does not mean that acitretin will not work for you, but inform your doctor if this happens. Continue to take acitretin even if you feel well. Do not stop taking acitretin without talking to your doctor.

After you stop taking acitretin, your symptoms may come back. inform your doctor if this happens. Do not use leftover acitretin to treat a new flare-up of psoriasis. A different medication or dose may be needed.

Other uses for this medicine

Acitretin is sometimes also used to treat Darier's disease (a type of skin disease); palmoplantar pustulosis (pus-filled blisters and red patches on the hands and feet); lichen sclerosus et atrophicus of the vulva (redness, scaling, and easy bleeding of the genital area in females); palmoplantar lichen nitidus (clusters of bumps on the hands and feet); and lichen planus (red, itchy bumps in various places on the body). It is also used to treat lamellar ichthyosis (scaly patches of skin that fall off the body); Sjogren-Larsson syndrome (dry, scaling skin, mental retardation, and trouble walking); and bullous and nonbullous ichthyosiform erythroderma (red, blistering, or peeling skin) in children. Talk to your doctor about the possible risks of using this drug for your condition.

This medication may be prescribed for other uses; ask your doctor for more information.

What special precautions to follow?

Before taking acitretin,

inform your doctor if you are allergic to acitretin, other retinoids such as adapalene (Differen), alitretinoin (Panretin), etretinate (Tegison), isotretinoin (Accutane), tazarotene (Tazorac), tretinoin (Renova, Retin-A, Vesanoid), vitamin A, or any other medications.

do not take methotrexate (Rheumatrex, Trexall) or tetracycline antibiotics such as demeclocycline (Declomycin), doxycycline (Doryx, Vibramycin), minocycline (Dynacin, Minocin), and tetracycline (Sumycin) while taking acitretin.

inform your doctor what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention the medications and herbs listed in the IMPORTANT WARNING section and any of the following: glyburide (Diabeta, Glynase, Micronase), other oral retinoids such as isotretinoin (Accutane) and tretinoin (Vesanoid), phenytoin (Dilantin, Phenytek), and vitamin A. Also inform your doctor if you have ever taken etretinate (Tegison). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.

inform your doctor if you have or have ever had the conditions mentioned in the IMPORTANT WARNING section; if you drink large amounts of alcohol; if you have a family history of high cholesterol or diabetes; if you have or have ever had diabetes, high cholesterol or triglycerides, spinal problems, depression, or stroke or mini-stroke; or if you have or have ever had joint, bone, kidney, or heart disease.

do not breast-feed while taking acitretin or if you have recently stopped taking acitretin.

you should know that acitretin may limit your ability to see at night. This problem may begin suddenly at any time during your treatment. Be very careful when driving at night.

plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Do not use sunlamps while taking acitretin. Acitretin may make your skin sensitive to sunlight.

if you need to have phototherapy, inform your doctor that you are taking acitretin.

you should know that acitretin may dry your eyes and make wearing contact lenses uncomfortable during or after treatment. Remove your contact lenses and call your doctor if this happens.

What special dietary instructions to follow?

Unless your doctor informs you otherwise, continue your normal diet.

What to do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can this medication cause?

You may experience hypoglycemia (low blood sugar) while you are taking this medication. Your doctor will inform you what you should do if you develop hypoglycemia. He or she may inform you to check your blood sugar, eat or drink a food or beverage that contains sugar, such as hard candy or fruit juice, or get medical care. Follow these directions carefully if you have any of the following symptoms of hypoglycemia:

shakiness

dizziness or lightheadedness

sweating

nervousness or irritability

sudden changes in behavior or mood

headache

numbness or tingling around the mouth

weakness

pale skin

hunger

clumsy or jerky movements

If hypoglycemia is not treated, severe symptoms may develop. Be sure that your family, friends, and other people who spend time with you know that if you have any of the following symptoms, they should get medical treatment for you immediately.

confusion

seizures

loss of consciousness

Acitretin can also cause hyperglycemia (high blood sugar). Call your doctor immediately if you have any of the following symptoms of hyperglycemia:

extreme thirst

frequent urination

extreme hunger

weakness

blurred vision

If high blood sugar is not treated, a serious, life-threatening condition called diabetic ketoacidosis could develop. Call your doctor immediately if you have any of the these symptoms:

dry mouth

nausea and vomiting

shortness of breath

breath that smells fruity

decreased consciousness

Acitretin may cause other side effects. inform your doctor if any of these symptoms are severe or do not go away:

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them or those listed in the IMPORTANT WARNING section, call your doctor immediately:

rash

headache

nausea

vomiting

blurred vision

pain, swelling, or redness of eyes or eyelids

eye pain

eyes sensitive to light

swelling of hands, feet, ankles, or lower legs

redness or swelling in one leg only

depression

thoughts of hurting or killing yourself

bone, muscle, or back pain

difficulty moving any part of your body

loss of feeling in hands or feet

chest pain

slow or difficult speech

rash

tingling in arms and legs

loss of muscle tone

weakness or heaviness in legs

confusion

cold, gray skin

slow or irregular heartbeat

pale skin

dizziness

fast heartbeat

weakness

shortness of breath

Acitretin may cause bone problems and slowing or stopping of growth in children. Talk to your child's doctor about the risks of giving this medication to your child.

Acitretin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

What to know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose

In case of overdose, consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.

Symptoms of overdose may include:

headache

dizziness

vomiting

upset stomach

dry, itchy skin

loss of appetite

bone or joint pain

If a female who could become pregnant takes an overdose of acitretin, she should take a pregnancy test after the overdose and use two forms of birth control for the next 3 years.

What other information to know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to this medicine.

Do not let anyone else use your medication. If you still have symptoms and need further treatment, consult your doctor.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Ref: U.S. National Library of Medicine.

This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.